The treatment of microbial infections is increasingly complicated by the ability of certain microbes (e.g., bacteria) to develop resistance to anti-microbial agents.
Of particular concern are hospital-contracted, or nosocomial infections, which exhibit antibiotic resistance. Streptococcus pneumoniae, for example, causes approximately 3,000 cases of meningitis, 50,000 cases of bacteremia, 500,000 cases of pneumonia, and nearly 7,000,000 cases of otitis media in the United States, in addition to being a leading cause of mortality. Antibiotic resistant strains of Streptococcus have emerged and are now becoming widespread in certain communities. While vancomycin remains effective at treating the vast majority of Streptococcus infections, vancomycin resistant strains have already been identified (see, for example, Archer et al. (1994) Antimicrob. Agents Chemother. 33(4):791-793).
Escherichia coli O157:H7 (herein referred to as O157:H7) is an emerging cause of food borne illness. The CDC estimates that there are approximately 73,000 cases of infection and 61 deaths in the United States each year. Infection has a range of consequences from bloody diarrhea to occasional kidney failure. Most illness has been associated with eating undercooked, contaminated ground beef. Infection can also occur after drinking unpasteurized milk. In addition, other microbial pathogens, such as Salmonella, Shigella, Listeria, and Campylobacter, are also potential food product contaminants and are known to cause serious disease in humans (Tauxe R. V. (2002) Int. J. Food Microbiol. 78(1-2):31-41; Mead et al. (1999) Emerg. Infect. Dis. 5(5):607-625). At present there is no effective conventional antibiotic treatment for O157:H7, and drug-resistant Campylobacter infections (for example, macrolide-resistant Campylobacter) are becoming increasingly common (Gibreel et al. (2006) J. Antimicrob. Chemother. May 30). While one strategy to combat food contamination has been to add antibiotics to livestock feed, this has resulted in high levels of antibiotic resistant bacteria which ultimately endangers both livestock and humans. In addition, such antibiotic resistance decreases the value of certain antibiotics for use in humans (Phillips et al. (2004) J. Antimicrob. Chemother. 53(1):28-52).
Thus, not only is there a need for new antibiotics which can treat specific, drug-resistant nosocomial (e.g., Streptococcus) and food-borne pathogens (e.g., 0157:H1 and Campylobacter), but also for alternative strategies for preventing or destroying microbial infections of food, for example, through direct treatment of food products.
Glucosinolates and their breakdown products—isothiocyanates (ITCs) are secondary metabolites, actively used by certain plants for the defense against natural pathogens (Fenwick et al. (1983) Crit. Rev. Food Sci. Nutr. 18:123-201; Delaquis et al. (1995) Food Technol. 73-84; Osbourn et al. (1996) Plant Cell 8:1821-1831; Fahey et al. (2001) Phytochemistry 56:5-51). These compounds are commonly found in and enriched in the plant family Cruciferae, which includes, for example, broccoli, cabbage, watercress, and Brussel sprouts). These vegetables are widely consumed by humans.
Despite their history of use in folk medicine, evaluation of ITCs as potential anti-pathogens has been limited, potentially due to relatively low activity of test compounds (Tajima et al. (2001) Biosci. Biotechnol. Biochem. 65:1886-1888; Tajima et al. (2003) Biosci. Biotechnol. Biochem. 67:1844-1846; and Fahey et al. (2002) Proc. Natl. Acad. Sci. USA 99:7610-7615).